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Although microglia are largely responsible for injury-induced inflammatory response, they play beneficial roles in both normal and disease states. However, the effects of microglial depletion on neonatal HIE remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Tamoxifen was administered to Cx3cr1\n                      <jats:sup>CreER\/+<\/jats:sup>\n                      Rosa26\n                      <jats:sup>DTA\/+<\/jats:sup>\n                      (microglia-depleted model) and Cx3cr1\n                      <jats:sup>CreER\/+<\/jats:sup>\n                      Rosa26\n                      <jats:sup>DTA\/\u2212<\/jats:sup>\n                      (control) mice at P8 and P9 to assess the effect of microglial depletion. The density of microglia was quantified using Iba-1 staining. Moreover, the proportion of resident microglia after the HI insult was analyzed using flow cytometric analysis. At P10, the HI insult was conducted using the Rice-Vannucci procedure at P10. The infarct size and apoptotic cells were analyzed at P13. Cytokine analyses were performed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) at P13.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At P10, tamoxifen administration induced &gt;\u200999% microglial depletion in DTA\n                      <jats:sup>+<\/jats:sup>\n                      mice. Following HI insult, there was persisted microglial depletion over 97% at P13. Compared to male DTA\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice, male DTA\n                      <jats:sup>+<\/jats:sup>\n                      mice exhibited significantly larger infarct volumes; however, there were no significant differences among females. Moreover, compared to male DTA\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice, male DTA\n                      <jats:sup>+<\/jats:sup>\n                      mice had a significantly higher density of TUNEL\n                      <jats:sup>+<\/jats:sup>\n                      cells in the caudoputamen, cerebral cortex, and thalamus. Moreover, compared to female DTA\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice, female DTA\n                      <jats:sup>+<\/jats:sup>\n                      mice showed a significantly greater number of TUNEL\n                      <jats:sup>+<\/jats:sup>\n                      cells in the hippocampus and thalamus. Compared to DTA\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice, ELISA revealed significantly lower IL-10 and TGF-\u03b2 levels in both male and female DTA\n                      <jats:sup>+<\/jats:sup>\n                      mice under both normal conditions and after HI (more pronounced).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We established a microglial depletion model that aggravated neuronal damage and apoptosis after the HI insult, which was predominantly observed in males.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-020-01792-7","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T22:02:39Z","timestamp":1586556159000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Aggravated brain injury after neonatal hypoxic ischemia in microglia-depleted mice"],"prefix":"10.1186","volume":"17","author":[{"given":"Shunichiro","family":"Tsuji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Di Martino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Mukai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoko","family":"Tsuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klas","family":"Blomgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrika","family":"\u00c5den","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,11]]},"reference":[{"key":"1792_CR1","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s11481-012-9347-2","volume":"8","author":"C Kaur","year":"2013","unstructured":"Kaur C, Rathnasamy G, Ling EA. 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